Production of dioximes and isoxazoles



Patented Oct. 21, 1941 PRODUCTION OF DIOXIMES AND ISOX- AZOLES Samuel B. Lippincott, Terre Haute, Ind., assignor to Commercial Solvents Corporation, Terre Haute, Ind., a corporation of Maryland No Drawing. Application July 8, 1940, Serial No. 344,371

4 Claims.

My invention relates to the production of isoxa zoles from nitroparaffins, and to the production of dioximes as intermediate products in this process. My invention also relates to new compositions of matter comprising intermediate and final products of this process.

It has previously been known that nitroparaffins containing more than one carbon atom could be transformed to isoxazoles by the action of alkali at elevated temperatures. (Dunstan et al., J. of Chem. Soc. 59, 410). The isoxazoles produced from the lower nitroparafiins by this method are liquid products which are difficult to purify without decomposition. As a result, relatively low yields have been obtained by this process.

I have now discovered that by suitably con- The production of the dioximes mey be effected by maintaining the reaction temperature sufficiently low to prevent substantial hydrolysis of the dioxime to the isoxazole. strong alkalies have a greater tendency to promote the second stage of this reaction than weak alkalies, and that it is more difficult to terminate the reaction with the production of dioximes when strong alkalies are employed, even when using relatively low temperatures. I prefer, therefore, to utilize weaker alkaline condensation agents, and especially ammonia bases, for effecting this reaction. The term ammonia base, as used herein and in the appended claims signifies ammonia and compounds in which one or more hydrogens of the ammonia may be substituted by neutral or basic aliphatic groups. Alkyl amines such as ethyl amine, diethyl amine, triethyl amine, propyl amines, butyl amines, and the'like, are very satisfactory for this purpose. It is to be understood, however, that the alkyl amines are merely preferred alkaline condensation agents, and that other bases of equivalent alkalinity may be employed satisfactorily. The

I have found that amount of alkaline condensation agent to be employed may vary within relatively wide limits. There is reason to believe that the mechanism of this reaction involves the neutralization of 1 mole of nitric acid per mole of dioxime formed.

For this reason it is desirable to employ at least one-third equivalent of alkaline material. per, mole of nitroparaflin. An excess of a relatively weak base is not detrimental, and in general I prefer to employ at least 1 mole of an alkyl amine or equivalent alkaline-converting'agentper mole of nitroparafiin.

The production of the dioximes is preferably effected in a solvent medium, which is, a common solvent for the nitroparaffin and-alkali or the resulting nitroparaflin salt, and in which the I dioxime is relatively insoluble. Water constitutes a very satisfactory solvent medium,- especially for the production of dioximes from the lower nitroparaflin's. It is obvious, however, that other solvents having the above characteristics may be employed in place of water. The amount of solvent to be employed is not critical. I have effected the reaction in the absence of any solvent, and in the presence of water in amounts varying from one-fourth mole of water per mole of nitroparaflin to fifty moles of water per mole of nitroparaflin, obtaining dioximes in all cases. I prefer, however, to employ from 0.25 to 5.0 moles of water per mole of' nitroparaffin', in most cases.

The production of the dioximes should'be effected at relatively low temperatures, 'i.he.,below 50 C., and preferably at temperatures of "-10" C. to +30 C. Low temperatures facilitate stopping the reaction at the dioxime' stage, especially in the case of the lower molecularweightnitroparafiins. When reacting low molecular weight nitroparafiins, and especially nitroethane, I prefer to employ temperatures below ordinary room temperatures. The formation of the dioximes is evidenced by the appearance of a crystalline precipitate, whereas the isoxazoles prepared from cipitate.

the mixture to stand at reaction temperature until the reaction is complete, as evidenced by the formation of no further crystalline pre- The reaction can, however, be initiated at a somewhat higher temperature than the desired reaction temperature, and then cooled to reaction temperature for the completion of the reaction. Thus I have allowed reaction mixtures of this type to stand at room temperature for an initial period, and then completed the reactions at approximately C.

Any of the primary nitroparafiins which con tain more than one carbon atom maybe transformed into dioximes by myprocess. 'Mixed, nitroparafllns may be employed if desired, but

the resulting mixture of the various possible di-' oximes will present difiiculties in'separatingthe pure products, and I therefore prefer to usefia single nitroparafiin to produce a single sym-- metrical dioxime. The dioximes, obtained as described above, have the following type formula:

'I' haveifoundthat reaction proceeds in most caseswith quantitative yieldsof'both-isoxazo1e -andhy'droxylamm'onium salt. 1 'Thevhydrolysis" of these dioxim'es may be 'e'lfected 'inaccordance' with known "procedures for'ithe hydrolysis of other oximes, and myinyen'tion is not limitedto specific procedures for this step of/the process. I prefer,-however, to :carry-outthe.hydrolysis'by means of relatively Example I Nitroethane, diethylamine and water were mixed in the ratio of 1 mole of nitroethane, 1 mole of diethylamine and one-fourth mole of water, and the mixture was allowed to stand at 0 C. Crystallization of the dioxime was initiated by seeding, and at the conclusion of crystal formation, the crystals were separated by filtration and purified by successive recrystallizations from methanol.

The crystals thus obtained constituted 3- methyl-2,4-pentanedione dioxime (melting point -132. 0.; nitrogen content 19.64%;

nitrogen content 19.44%). also obtained utilizing n-propylamine as the altheoretical This product was kaline condensation agent, and the two products dilute aqueous solutions of a mineral acid, for

example, sulfuric acid of1l N to 5 N concentration. This reaction may suitably be carried out at the reflux temperature of the mixture, and the conclus'ioii .of the reaction is evidenced by the disappearance of the crystalline dioxime'and the appearance of the'isoxazole in the form of an oily .layerconstituting a second liquidphase. This oily-layerinay berecovered by decantation, and 'constitutesrelatively pure isoxazole if purified dioxime is employed in the reaction. The isoxazole thus ,obtained may be "further purifiedby vacuum jdistillation, if desired. The aqueous :layer of 'the'reaction product contains the hydroxylammoniumfsalt which may be recovered by vevaporation and crystallization.

My-inventionimay be further illustrated by the :followingj'specific examples:

Refractive index n were found to be identical by determining the melting point of a mixture of the products.

Thevpurified dioxime. thus obtained was converted to ,3,4,5-trimethylisoxazole by refluxing with dilute sulfuric acid. The hydroxylamine obtained as the second product of this hydrolysis amounted to 23.2% by weight of the dioxime (theoretical 22.9%), indicating 94.5%v conversion of the dioxime to the isoxazole.

Example II A mixture of l-nitropropane, n-propylamine andwater, in the ratio of onemole of nitropropane, one mole of n-propylamine and'one-jfourth mole of water was prepared and allowed to stand at room temperature,

Crystallization ensued Without seeding, and at the conclusion of. crystal growth the mixture was cooled to .0? C,, and filtered. The crystals were washed with Water, and the wash water. was added to the mother liquor, the resulting mixture being cooled to 0 C. to secure a second crop of crystals, The product, 4-ethyl-3,5-heptanedione dioxime, was obtained in a yield of 58% of thetheoreticalyield. After purification I by recrystallization from methanol the product was found to have a melting point of .2 -135.6 C. This product was also prepared by the use of ammonia, .n-butylamine, and 2-aminoheptane as the alkaline condensation agents, and in each case was foundibythe determination of a mixed melting point'to be identical with the above product.

The dioxime, prepared asabove described, was refluxed for 4 hourswith approximately twice its weight. of 3 N sulfuric acid. The resulting oily layer was separated by de'cantation and washed with water.v This material, which constituted 3,4,5-triethylisoxazole, wasobtained in an apparent yield of 102% of the theoretical yield. A

determination of hydroxylamine in the aqueous layer of the product indicated a theoretical yield of the hydroxylammonium salt. H

The isoxazole was vacuum distilled and'identified as 3,4,5-triethylisoxazole by the following properties:

Nitrogen content per cent 9.17(theoretical 9.15) Boiling point, 760 mm 215.3 C. Specific gravity, 20/'20 0.9363

Example III A mixture of l-nitrobutane, n-butylamine,' and water, in the proportions of 1 mole of l-nitrobutane, 1 mole of n-butylamine, and one-fourth mole of water was allowed to stand at room tem- Crystal formation ensued without the mixture was cooled to C., and allowed to stand at this temperature until the conclusion of further crystal growth. The crystals were recovered by filtration, and the mother liquor was again cooled to 0 C., to obtain a second crop of crystals. The product, -propyl-4,6-nonanedione dioxime, was obtained in a yietld of 37% of the theoretical yield. After recrystallization from methanol this compound was found to have a melting point of 116.4-116.8 C., and a nitrogen content of 12.19% (theoretical 12.27%).

The dioxime prepared as described above was refluxed for 6 hours with approximately six times its wetight of 2 N sulfuric acid. The resulting oily layer was separated by decantation and washed with water. This product, constituting 3,4,5-tripropylisoxazole, was obtained in an apparent yield of 102% of the theoretical yield. A determination of hydroxylamine in the aqueous layer of the product indicated a yield of 96% of the theoretical yietld of hydroxylamine sulfate.

The 3,4,5-tripropylisoxazole was further purified by vacuum distillation, and was found to have the following properties:

7.11 (theoretical for tripropyl isoxazole 7.16) Boiling point, 760 mm 255.2-255.6 C. Specific gravity, 20/20 0.9128 Refractive index n? 1.46088 It is to be understood, of course, that the above examples are merely illustrative, and do not limit Nitrogen content, per cent the scope of my invention. My invention is generally applicable to the production of dioximes and isoxazoles from any of the primary nitroparaflins (l-nitroalkanes) containing more than one carbon atom. As has previously been pointed out, other alkaline condensation agents might be employed in place of the specific amines employed in the examples, and the reaction conditions utilized in the examples could be varied in numerous respects. In general it may be said that the use of any equivalents or modifications of procedure which would naturally occur to those skilled in the art, is included within the scope of my invention.

My invention now having been described, what I claim is:

1. In a process for the production of isoxazoles from l-nitroalkanes containing more than one carbon atom, the steps which comprise condensin'g said l-nitroalkanes in the presence of an ammonia base, at a temperature sufliciently low to prevent substantial isoxazole formation, and subjecting the resulting crystalline product to hydrolysis.

2. In a process for the production of an isoxazcle from a l-nitroalkane containing from 2 to 4 carbon atoms, the steps which comprise condensing said l-nitroalkane in the presence of an aqueous solution of an alkylamine, at a temperature of 10 C. to +30 C., purifying the resulting dioxime, and subjecting said dioxime to acid hydrolysis to form the corresponding isoxazole.

-3. A process for the production of dioximes from l-nitroalkanes containing more than 1 carbon atom, which comprises condensing said 1- nitroalkanes in the presence of an ammonia base, at a temperature sufliciently low to prevent substantial isoxazole formation.

4. A process for the production of a dioxime from a. l-mtroalkane containing from 2 to 4 carbon atoms, which comprises condensing said'lnitroalkane. in the presence of an aqueous solution of an alkylamine at a temperature of 10 C. to +30 C.

SAMUEL B. LIPPINCOTT. 

